[CONTRIBUTION
FROM THE
EXTOMOLOGY RESEARCH BRANCH, AGRICULTURAL RESEARCH SERVICE, u. s. DEPARTMENT O F AGRICULTURE]
The Synthesis of 3-Piperonyltetrahydrofuran B. H. ALEXANDER
AND
W. F. BARTHEL
Received Apiil 11, 1956
3-Piperonyltetrahydrofuran and 10 related compounds have been synthesized for testing as potential synergists for pyrethrins against house flies.
Sesamin (I) increases the effectiveness of pyrethrins as a fly spray1 without itself showing any toxic action. I n seeking other synergistic materials of this type, which are more soluble in the hydrocarbon solvents in common use, LaForge and coworkers2 attempted the synthesis of the halfsesamin molecule (11). They prepared aZpha-(3chloropropy1)piperonyl alcohol (111), but all attempts to cyclize I11 and related compounds resulted in the formation of alpha-allylpiperonyl alcohol (IT) instead of the corresponding furan (11). It seems that the difficulty in the synthesis of I1 may be due to molecular strain, since the corresponding pyran (V), which is an effective synergist
I
11 H
I11 H
H
IV
--
VI
0
H
CH?
H
VI1
I
H&
CH,
,
I
CH?OH HOCH?
VI11
IX
for pyrethrins, mas synthesized3 in three steps from piperonal, ethyl acetate, and trimethylene bromide. This Iiaper outlines the synthesis of the substituted compound VI, in which the furan ring is attached to the methylenedioxyphenyl group through a methylene group at the 3 position of the furan ring. It also describes the synthesis of several related diesters of piperonylidene and piperonylsuccinic acid which were of interest since these compounds had not been previously reported and their insecticidal activity was unknown. The monoethyl ester of piperonylidenesuccinic acid (VII, R = H, R’ = C2Hs)was prepared as described by Cornforth, Hughes, and Lions.4 The monomethyl, monopropyl, dietJhyl, and dipropyl esters of piperonylidenesuccinic acid (VII, R = H, alkyl; R’ = alkyl) were synthesized also, as well as similar esters of piperonylsuccinic acid by hydrogenation of VII. Lithium aluminum hydride reduction of the monoesters or diesters of T’II gave the unsaturated 2-piperony lidene-l ,4-butanediol (YIII) in 85% yield. This was surprising, since Systrom and Brown6 reported that cinnamic acid on treatment with lithium aluminum hydride undergoes concurrent reduction a t the double bond producing hydrocinnamyl alcohol. When t,he 2-piperonylidene-l,4-butanediol (VIII) was dissolved in ether and treated with dry hydrogen chloride a t 0” or refluxed with 6% methanolic hydrogen chloride, 3(3) LaForge, U. S. Patent 2,421,570 (1947). (4) Cornforth, Hughes, and Lions, J . Proc. Roy. Soc. N . S. Wales, 72, 228 (1938). (5) Nystrom and Brown, J . Am. Chem. SOC.,69, 2548, 1197 (1947).
( I ) Haller, LaForge, and Sullivan, J . Org. Chem., 7, 185 (1942); Beroza and Schechter, J . Am. Chem. SOC., in press. (2) LaForge, Barthel, and Bendigo, unpublished work. 1302
OCTOBER
1956
1103
SYNTHESIS OF 3-PIPEROKYLTETRSHYDROFURBPI'
piperonylidenetetrahydrofuran (IX) was produced. Hydrogenation of IX a t 1 atmosphere with a platinum oxide catalyst yielded 3-piperonyltetrahydrofuran (VI). An attempt was made to synthesize T'I by the following series of reactions : Diethyl piperonylidenesuccinate (T'II)was hydrogenated under pressure with a nickel-kieselguhr catalyst,6and the resulting diester was reduced with lithium aluminum hydride to piperonylbutanediol (VI11 saturated at double bond). When 2-piperonyl-l,4-butanediol was dissolved in ether and treated with hydrogen chloride or refluxed with methanolic hydrogen chloride, a mixture of compounds isomeric with VI resulted. EXPERIMENTAL
T h e monomethyl ester of piperonylidenesuccinic acid (VII, = H, R' = CHI) was prepared by the method of Cornforth, Hughes, and Lions;4 m.p. 136-138' recrystallized from benzene; yield 56%. Anal. Calc'd for C13H1206: C, 59.09; H, 4.58. Found: C, 59.17; H, 4.59. The dimethyl ester of piperonylidenesuccinic acid (VII, R and R' = CH3) was prepared from the monomethyl ester by refluxing with methanol containing 6% sulfuric acid; m p. 83-84' recrystallized from methanol; yield 59%. A n a l . Calc'd for C14H1406: C, 60.43; H, 5.07. Found: C, 60.39; H, 5.01. T h e diethyl ester of piperonylidenesuccinic acid (VII, R and R' = C2Hs) was prepared as described for the dimethyl ester above or via the acid chloride; b.p. 184-191"/0.3 mm.; n'," 1.5512; yield 29% via the acid chloride or 59% by the former procedure. Anal. Calc'd for C16HleOs:C, 62.74; H, 5.92. Found: C, 63.49; H, 6.20. T h e monopropyl ester of piperonylidenesuccinic acid (VII, R = H, R' = C3Hi) was prepared by the method of Corn; ~ 120-121' recrvstallized from benzene: forth, el ~ 1 . m.p. yield 5 1%. A n a l . Cillc'd for ClSHI6O6: C, 61.64; H, 5.52. Found: C, 61.85: H. 5.24. The dimethyl ester of piperonylszrccinic acid was prepared by hydrogenating the unsaturated ester (VII) in alcohol, with a nickel-kieselguhr catalyst,e under pressure; b.p. 160163"/0.3 mm.; n'r: 1.5133; yield 91%.
R
(6) Covert, Connor, and Adkins, J . Am. Chem. Soc., 54, 1651 (1932).
Anal. Calc'd for C~Hl606:C, 59.99; H, 5.76. Found: C, 60.04: H, 5.55. The diethyl ester of piperonylsuccinic acid was prepared as described for the dimethyl ester above; b.p. 159-164"/0.3 mm.; n'z 1.5032; yield 89%. A n a l . Calc'd for C16H2006: C, 62.32; H, 6.54. Found: C, 62.27; H, 6.39. The dipropyl ester of piperonylsuccinic acid TI-asprepared as above; b.p. 180-186"/0.04 mm.; n*z 1.4947; yield 90%. Anal. Calc'd for C&&: C, 64.27:, H,. 7.19. Found: C. 64.09; H, 7.32. 2-PiperonyZidene-l,4-butanediol(VIII) . Diethyl piperonylidenesuccinate was reduced with lithium aluminum hvdride:6 m.p. 85-86' recrystallized from benzene; yield 85%. The compound reduced a 1% potassium permanganate solution. Anal. Calc'd for C12Hi404: C, 64.85; >I, 6.35. Found: C, 65.10; H, 6.44. 2-Piperonyl-l,4-butanediol. 2-Piperonylidene-1,4-hutanediol (VIII) was dissolved in alcohol and hydrogenated with a nickel-kieselguhr catalyst, under pressure; b.p. 190"/0.6 mm.; n'r: 1.5493; yield 92%. Anal. Calc'd for C12H1604: C, 64.27; H, 7.19. Found: C , 64.29; H, 7.40. 3-Pzperon ylidenefetrahydrof uran (IX) 2-Piperonylidene1,Cbutanediol (VIII), 6 g., was refluxed in 200 ml. of 6% methanolic hydrogen chloride for 6 hours. After standing a t 5" overnight, the solution tyas neutralized vith 5% sodium carbonate and concentrated in vacuo to one-third the original volume, which then was extracted with ether and the ether layer washed with cold R-ater. After removal of the ether, the residue was distilled; b.p. 135-137'/1.3 mm.; nzz 1.5603; yield 65%. This compound gave no test for active hydrogen with Grignard reagent (Zerewitinoff method), but it reduced a 1% potassium permanganate solution. A n a l . Calc'd for C12H1203: C, 70.57; H, 5.92. Found: C, 69.86; H, 5.77. S-Piperonyltetrahydro~riran (TI). Piperonylidenetetralivdrofuran (IX), 2 g., was dissolved in alcohol. A platinum oxide catalyst, 0.1 g., was added and the mixture was hydrogenated a t one atmosphere. After removal of solvent the residue was distilled; b.p. 108"/1 mm.; nz: 1.5380; yield 70'%. This compound gave no test for active hydrogen nor did it reduce potassium permanganate solution. Anal. Calc'd for C , ~ H I ~ C, O ~69.88; : H, 6.84. Found: C, 69.93; H, 7.01.
.
Acknowledgment. The helpful suggestions of hlr. Martin Jacobson of this laboratory are gratefully acknowledged. All microanalyses were performed by Miss Kathryn Gerdeman, of the Chemistry Department, University of Maryland. BELTSVILLE, MARYLAND
